The objectives of this proposal are: 1) To test the hypothesis that survival of the kidney and bone marrow grafts in human is related to the recipients to hepatitis B infection before transplantation. 2) To gain insight into the mechanism by which responses to hepatitis B virus (HBV) might be related to responses to organ grafts. Specifically, to test the hypothesis that there is cross reactivity between an antigenic determinant on HBV and a male associated antigen. Preliminary observations of human kidney and bone marrow grafts suggest that recipients with antibody (anti-HBs) to the surface antigen of HBV (HBsAg) are likely to reject such grafts within six months of transplatation, particularly if the organ donor is a male. These and other epidemiological and experimental studies are consistent with the hypothesis stated above. We plan to test this hypothesis by: 1) Extending the clinical and epidemiological studies of kidney and bone marrow transplantation in relation to the responses of graft recipients to hepatitis B infection before transplantation; 2) By investigating whether the postulated cross reacting antigen is present on sperm as shown by an association between antibodies to HBV and antisperm antibodies in humans (vasectomized men) or experimental animals; and 3) By studying in in-bred mice the mechanism of early rejection of male to female skin grafts from male donors by female recipients immunized against HBsAg.